A large erythroid spectrin beta-chain variant.

Abstract

A large variant of erythrocyte beta-spectrin was found in a child presenting with hereditary elliptocytosis and anaemia. This polypeptide was phosphorylated, cross-reacted with normal beta-spectrin in immunoblotting and formed a dimer with alpha-spectrin that co-purified with normal alpha beta dimer. The molecular weight was estimated to be 330 kD by SDS gel electrophoresis, which is 84 kD (35%) larger than the normal beta-chain. This variant has been tentatively named spectrin Detroit (beta Detroit). Tryptic digests demonstrated a coexisting alpha-spectrin variant Sp alpha I/65 in the propositus, his father and a paternal uncle. Anaemia and elliptocytosis was associated with Sp alpha I/65 rather than beta Detroit, since other family members with beta Detroit in whom alpha-spectrin was normal had no morphological or clinical abnormalities. Family members were identified who had normal alpha-spectrin but were heterozygotic for the large beta-spectrin. Their erythrocyte membranes were more rigid and fragile than normal. The fragility is probably a consequence of both weaker dimer association and spectrin deficiency. Variant spectrin dimers (alpha beta Detroit) had a reduced self-association constants. Binding to ankyrin was normal. Instability of beta Detroit during erythropoiesis is suggested by the fact that it comprises only 25% of the beta-spectrin in beta Detroit heterozygote erythrocytes, and total spectrin was reduced by 20%. Although beta Detroit has some functional defects, this 84 kDa insert in erythrocyte spectrin is compatible with nearly normal function.